INVESTIGATION OF THE ABILITY OF SEVERAL NATURALLY-OCCURRING AND SYNTHETIC POLYANIONS TO BIND TO AND POTENTIATE THE BIOLOGICAL-ACTIVITY OF ACIDIC FIBROBLAST GROWTH-FACTOR

The ability of several animal, plant, and bacterial derived polyanions (PAs) as well as synthetic PAs to compete with heparin for the bindin g of acidic fibroblast growth factor (aFGF) was correlated with their ability to potentiate the mitogenic and neurotrophic actions of this f actor. Dextran sulphate, kappa-carrageenan, pentosan sulphate, polyane thole sulfonate, heparin, and fucoidin competed for the heparin bindin g site on aFGF at relatively low concentrations (<50 mug/ml). Lambda-c arrageenan, iota-carrageenan, and polyvinyl sulphate exhibited lower a ffinity for aFGF, whereas hyaluronic acid, dermatan sulphate, chondroi tin-6-sulphate, chondroitin-4-sulphate, and uncharged dextran displaye d very low or no demonstrable affinity. Potentiation of the mitogenic action of aFGF for Balb/c 3T3 fibroblasts tended to be in general agre ement with the aFGF binding affinity of the PAs. However, polyanethole sulfonate, the carrageenans, polyvinyl sulphate, fucoidin, and pentos an sulphate exerted a mitogenic action on the 3T3 cells that was indep endent of, and in addition to, the ability of these GAGs to potentiate the action of aFGF. The ability to potentiate the neurotrophic action of aFGF for E8 chick ciliary neurons was a general property of those PA with low or no activity in the mitogen assay. Thus hyaluronic acid, dermatan sulphate, chondroitin-4-sulphate, chondroitin-6-sulphate, an d even uncharged dextran all potentiated aFGF induced neuronal surviva l. The differential effects of these PA in potentiating the biological activities of aFGF are discussed in relation to their ability to comp ete for the heparin-binding site of aFGF. (C) 1993 Wiley-Liss, Inc.